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Key words: Analgesia. Practice guidelines: analgesia; sedation. Sedation: conscious.
ANESTHESIOLOGISTS possess specific expertise in the pharmacology, physiology, and clinical management of patients receiving sedation and analgesia. For this reason, they are frequently called on to participate in the development of institutional policies and procedures for sedation and analgesia in nonoperating-room settings. To assist in this process, the American Society of Anesthesiologists developed these Guidelines for Sedation and Analgesia by Non-Anesthesiologists.
Practice guidelines are systematically developed recommendations that assist practitioners in making decisions about health care. These recommendations may be adopted, modified, exceeded, or rejected according to clinical needs and constraints, and they are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. Practice guidelines are not intended as standards or absolute requirements, and their use cannot guarantee any specific outcome.
The practice guidelines enumerated below have been developed using systematic literature summarization techniques. Results of the literature analyses have been supplemented by the opinions of the Task Force members and a panel of more than 60 consultants, drawn from a variety of medical specialties in which sedation and analgesia are commonly provided. In those instances when the literature does not provide conclusive data, there is an explicit statement that the guidelines are based on the opinion of the consultants or the consensus of the Task Force members. A detailed description of the analytic methods is included in appendix 1.
"Sedation and analgesia" describes a state that allows patients to tolerate unpleasant procedures while maintaining adequate cardiorespiratory function and the ability to respond purposefully to verbal command and/or tactile stimulation. The Task Force decided that the term "sedation and analgesia" (sedation/analgesia) more accurately defines this therapeutic goal than does the commonly used but imprecise term "conscious sedation." Note that patients whose only response is reflex withdrawal from a painful stimulus are sedated to a greater degree than encompassed by "sedation/analgesia."
The purpose of these guidelines is to allow clinicians to provide their patients with the benefits of sedation/analgesia while minimizing the associated risks. Sedation/analgesia provides two general types of benefit: First, sedation/analgesia allows patients to tolerate unpleasant procedures by relieving anxiety, discomfort, or pain. Second, in children and uncooperative adults, sedation/analgesia may expedite the conduct of procedures that are not particularly uncomfortable but require that the patient not move. Excessive sedation/analgesia may result in cardiac or respiratory depression that must be rapidly recognized and appropriately managed to avoid the risk of hypoxic brain damage, cardiac arrest, or death. Conversely, inadequate sedation/analgesia may result in undue patient discomfort or patient injury because of lack of cooperation or adverse physiologic response to stress.
These guidelines have been designed to be applicable to procedures performed in a variety of settings (e.g., hospitals, free-standing clinics, physicians' offices) by practitioners who are not specialists in anesthesiology. The guidelines specifically exclude the following: (1) patients who are not undergoing a diagnostic or therapeutic procedure (e.g., postoperative analgesia, sedation for treatment of insomnia); (2) otherwise healthy patients receiving peripheral nerve blocks, local or topical anesthesia, and/or no more than 50% N2O with oxygen and no other sedative or analgesic agents administered by any route; (3) situations when it is anticipated that the required sedation will eradicate the purposeful response to verbal commands or tactile stimulation (as distinct from reflex withdrawal from a painful stimulus); such patients require a greater level of care than recommended by these guidelines; and (4) perioperative management of patients undergoing general anesthesia or major conduction anesthesia (spinal or epidural/caudal blockade).
These guidelines are intended to be general in their application and broad in scope. The appropriate choice of agents and techniques for sedation/analgesia is dependent on the experience and preference of the individual practitioner, requirements or constraints imposed by the patient or procedure, and the likelihood of producing unintended loss of consciousness. Templates are provided as examples to illustrate principles; clinicians and their institutions have ultimate responsibility for selecting patients, procedures, medications, and equipment.
I. Patient Evaluation
Published data suggest and consultant opinion strongly supports the contention that appropriate preprocedure evaluation of patients' histories and physical findings reduces the risk of adverse outcomes. Additionally, consultant opinion supports the contention that an appropriate history, physical examination, and laboratory evaluation leads to improved patient satisfaction.
Recommendations: Clinicians administering sedation/analgesia should be familiar with relevant aspects of the patient's medical history including: (1) abnormalities of the major organ systems, (2) previous adverse experience with sedation/analgesia, as well as regional and general anesthesia, (3) current medications and drug allergies, (4) time and nature of last oral intake, and (5) history of tobacco, alcohol, or substance use or abuse. Patients presenting for sedation/analgesia should undergo a focused physical examination including auscultation of the heart and lungs and evaluation of the airway (Table 1template 1). Preprocedure laboratory testing should be guided by the patient's underlying medical condition and the likelihood that the results will affect the management of sedation/analgesia.
II. Preprocedure Preparation
Patient Counseling: There is insufficient evidence in the literature to establish the benefit of providing the patient (or her/his guardian, in the case of a child or impaired adult) with preprocedure information about sedation/analgesia. However, the consultants strongly support the contention that appropriate preprocedure counseling improves patient satisfaction and reduces risks; they also support the view that costs may be reduced. The Task Force members concur that patients undergoing sedation/analgesia should be informed of the benefits, risks, and limitations associated with this therapy, as well as possible alternatives.
Preprocedure Fasting: Because sedatives and analgesics tend to impair airway reflexes in proportion to the degree of sedation/analgesia achieved, members of the Task Force support the concept of preprocedure fasting before sedation/analgesia for elective procedures. However, the literature provides insufficient data to test the hypothesis that preprocedure fasting results in a decreased incidence of adverse outcomes in patients undergoing sedation/analgesia (as distinct from patients undergoing general anesthesia).
Recommendations: Patients (or their legal guardians in the case of minors or legally incompetent adults) should be informed of and agree to the administration of sedation/analgesia before the procedure begins. Patients undergoing sedation/analgesia for elective procedures should not drink fluids or eat solid foods for a sufficient period of time to allow for gastric emptying before their procedure (Table 2template 2). In urgent, emergent, or other situations when gastric emptying is impaired, the potential for pulmonary aspiration of gastric contents must be considered in determining the timing of the intervention and the degree of sedation/analgesia.
Level of Consciousness: The response of patients to commands during procedures performed with sedation/analgesia serves as a guide to their level of consciousness. Spoken responses also provide an indication that the patients are breathing. Patients whose only response is reflex withdrawal from painful stimuli are likely to be deeply sedated, approaching a state of general anesthesia, and should be treated accordingly. The consultants strongly support the contention that monitoring level of consciousness reduces risks and support the concept that overall costs may be reduced. The members of the Task Force believe that many of the complications associated with sedation/analgesia can be avoided if adverse drug responses are detected and treated in a timely manner (i.e., before the development of cardiovascular decompensation or cerebral hypoxia); this may pose a special risk to patients given sedatives/analgesics in unmonitored settings in anticipation of a subsequent procedure.
Pulmonary Ventilation: It is the opinion of the Task Force that a primary cause of morbidity associated with sedation/analgesia is drug-induced respiratory depression. The literature suggests and consultant opinion strongly supports the observation that monitoring of ventilatory function reduces the risk of adverse outcomes associated with sedation/analgesia. Ventilatory function usually can be effectively monitored by observation of spontaneous respiratory activity or auscultation of breath sounds. In circumstances where patients are physically separated from the caregiver, the consultants support and the Task Force members concur that automated apnea monitoring (by detection of exhaled carbon dioxide or other means) may decrease risks; the consultants suggest that such monitoring will not reduce overall costs. The Task Force cautions practitioners that impedance plethysmography may fail to detect airway obstruction.
Oxygenation: Published data suggest and the consultants strongly support the view that early detection of hypoxemia through the use of oximetry during sedation/analgesia decreases the likelihood of adverse outcomes, such as cardiac arrest and death. The literature suggests, the consultants strongly support, and Task Force members agree that hypoxemia during sedation and analgesia is more likely to be detected by oximetry than by clinical assessment alone. The Task Force emphasizes that oximetry is not a substitute for monitoring ventilatory function.
Hemodynamics: Although there is insufficient published data to reach a conclusion, it is the opinion of the Task Force that sedative and analgesic agents may blunt the appropriate autonomic compensation for hypovolemia and procedure-related stresses. Early detection of changes in patients' heart rate and blood pressure may enable practitioners to detect problems and intervene in a timely fashion, reducing the risk of cardiovascular collapse. The consultants support the concept that regular monitoring of vital signs reduces risks and suggest that it decreases costs. Although the literature provides no guidance, the consultants suggest the use of continuous electrocardiographic monitoring in patients with hypertension and strongly support its use in patients with significant cardiovascular disease or dysrhythmias; the consultants suggest that electrocardiographic monitoring is not required in patients without cardiovascular disease.
Recommendations: Monitoring of patient response to verbal commands should be routine, except in patients who are unable to respond appropriately (e.g., young children, mentally impaired or uncooperative patients) or during procedures in which facial movement could be detrimental. During procedures in which a verbal response is not possible (e.g., oral surgery, upper endoscopy), the ability to give a "thumbs up" or other indication of consciousness in response to verbal or tactile (light tap) stimulation suggests that the patient will be able to control his airway and take deep breaths if necessary. Note that a response limited to reflex withdrawal from a painful stimulus represents a greater degree of sedation/analgesia than addressed by this document.
Ventilatory function should be continually monitored by observation and/or auscultation. When ventilation cannot be directly observed, exhaled carbon dioxide detection is a useful adjunct to these modalities. All patients undergoing sedation/analgesia should be monitored by pulse oximetry with appropriate alarms. If available, the variable pitch "beep," which gives a continuous audible indication of the oxygen saturation reading, may be helpful. When possible, blood pressure should be determined before sedation/analgesia is initiated. Once sedation/analgesia is established, blood pressure should be measured at regular intervals during the procedure, as well as during the recovery period. Electrocardiographic monitoring should be used in patients with significant cardiovascular disease as well as during procedures in which dysrhythmias are anticipated.
IV. Recording of Monitored Parameters
Both the literature and consultant opinion suggest that contemporaneous recording of patients' level of consciousness, respiratory function, and hemodynamics reduces the risk of adverse outcomes. Although consultant opinion suggests that recording of this information may not improve patient comfort or satisfaction, the consultants suggest that it may reduce costs resulting from adverse events. The consultants strongly support recording of vital signs and respiratory variables before initiating sedation/analgesia, after administration of sedative/analgesic medications, at regular intervals during the procedure, on initiation of recovery, and immediately before discharge. It is the opinion of the Task Force that contemporaneous recording (either automatic or manual) of patient data provides information that could prove critical in determining the cause of any adverse events that might occur. Additionally, manual recording ensures that an individual caring for the patient is aware of changes in patient status in a timely fashion.
Recommendations: Patients' ventilatory and oxygenation status and hemodynamic variables should be recorded at a frequency to be determined by the type and amount of medication administered as well as the length of the procedure and the general condition of the patient. At a minimum, this should be: (1) before the beginning of the procedure, (2) after administration of sedative/analgesic agents, (3) on completion of the procedure, (4) during initial recovery, and (5) at the time of discharge. If recording is performed automatically, device alarms should be set to alert the care team to critical changes in patient status.
V. Availability of a Staff Person Dedicated Solely to Patient Monitoring and Safety
Although there are insufficient data in the literature to provide guidance on this issue, the Task Force recognizes that it is difficult for the individual performing a procedure to be fully cognizant of the patient's condition during sedation/analgesia. The consultants support the contention that the availability of an individual other than the person performing the procedure to monitor the patient's status improves patient comfort and satisfaction; they also strongly support the view that risks are reduced. The consultants support the observation that this would not decrease overall costs. It is the consensus of the Task Force members that the individual monitoring the patient may assist the practitioner with interruptible ancillary tasks of short duration once the patient's level of sedation/analgesia and vital signs have stabilized, provided that adequate monitoring is maintained.
Recommendations: A designated individual, other than the practitioner performing the procedure, should be present to monitor the patient throughout procedures performed with sedation/analgesia. This individual may assist with minor, interruptible tasks.
VI. Training of Personnel
Although there is insufficient literature to determine the effectiveness of training on patient outcomes, the consultants strongly support the observation that providing appropriate training in clinical pharmacology for individuals administering sedative/analgesic medications reduces the risk of adverse outcomes; they also support the views that patient comfort is improved and overall costs are reduced. Specific concerns include: (1) potentiation of sedative-induced respiratory depression by concomitantly administered opioids; (2) inadequate time intervals between doses of sedative or analgesic agents, resulting in a cumulative overdose; and (3) inadequate familiarity with the role of pharmacologic antagonists for sedative and analgesic agents.
Because the primary complications of sedation/analgesia are related to respiratory or cardiovascular depression, it is the consensus of the Task Force that the individual responsible for monitoring the patient should be trained in the recognition of complications associated with sedation/analgesia. In addition, at least one qualified individual, capable of establishing a patent airway and maintaining ventilation and oxygenation, should be present during the procedure.
Recommendations: Individuals responsible for patients receiving sedation/analgesia should understand the pharmacology of the agents that are administered, as well as the role of pharmacologic antagonists for opioids and benzodiazepines. Individuals monitoring patients receiving sedation/analgesia should be able to recognize the associated complications. At least one individual capable of establishing a patent airway and positive pressure ventilation, as well as a means for summoning additional assistance, should be present whenever sedation/analgesia is administered. It is recommended that an individual with advanced life-support skills be immediately available.
VII. Availability of Emergency Equipment
The literature suggests and the consultants strongly support the view that the ready availability of appropriately sized emergency equipment reduces the risk of sedation and analgesia. The consultants also support the contention that overall costs, including those associated with adverse outcomes, may be reduced. The literature does not address the need for cardiac defibrillators during sedation/analgesia. The consultants strongly support the availability of a defibrillator whenever sedation/analgesia is administered.
Recommendations: Pharmacologic antagonists as well as appropriately sized equipment for establishing a patent airway and providing positive pressure ventilation with supplemental oxygen should be present whenever sedation/analgesia is administered. Advanced airway equipment and resuscitation medications should be immediately available (Table 3template 3). A defibrillator should be immediately available when sedation/analgesia is administered to patients with significant cardiovascular disease.
VIII. Use of Supplemental Oxygen
The literature supports the use of supplemental oxygen during sedation/analgesia: There is a decreased incidence and severity of hypoxemia among sedation/analgesia patients given oxygen as compared to those breathing room air. However, it must be appreciated that, by delaying the onset of hypoxemia, supplemental oxygen will delay the detection of apnea by pulse oximetry, emphasizing the importance of monitoring pulmonary ventilation by other means (see above). Consultant opinion supports the view that supplemental oxygen decreases patient risk, while suggesting that routine use of supplemental oxygen may increase costs.
Recommendations: Equipment to administer supplemental oxygen should be present when sedation/analgesia is administered. If hypoxemia is anticipated or develops during sedation/analgesia, supplemental oxygen should be administered.
IX. Use of Multiple Sedative/Analgesic Agents
The literature supports the observation that combinations of agents may be more effective than single agents in certain circumstances. However, the published data also suggest and consultant opinion supports the observation that combinations of sedatives and opioids may increase the likelihood of adverse outcomes, including ventilatory depression and hypoxemia. Although not evaluated in the literature, it is the consensus of the Task Force that fixed combinations of sedative and analgesic agents may not allow the individual components of sedation/analgesia to be appropriately titrated to meet the individual requirements of the patient and procedure.
Recommendations: Combinations of sedative and analgesic agents should be administered as appropriate for the procedure being performed and the condition of the patient. Ideally, each component should be administered individually to achieve the desired effect (e.g., additional analgesic medication to relieve pain, additional sedative medication to decrease awareness or anxiety). The propensity for combinations of sedative and analgesic agents to potentiate respiratory depression emphasizes the need to appropriately reduce the dose of each component as well as the need to continually monitor respiratory function.
X. Titration of Sedative/Analgesic Medications to Achieve the Desired Effect
The literature suggests that the administration of small, incremental doses of intravenous sedative/analgesic drugs until the desired level of sedation and/or analgesia is achieved is preferable to a single dose based on patient size, weight, or age. The consultants support the concept that incremental drug administration improves patient comfort and decreases costs; they strongly support the contention that the potential risks associated with excessive doses are reduced.
Recommendations: Intravenous sedative/analgesic drugs should be given in small, incremental doses that are titrated to the desired endpoints of analgesia and sedation. Sufficient time must elapse between doses to allow the effect of each dose to be assessed before subsequent drug administration. When drugs are administered by nonintravenous routes (e.g., oral, rectal, intramuscular), allowance should be made for the time required for drug absorption before supplementation is considered.
XI. Intravenous Access
Published data suggest that, in cooperative patients, administration of sedative/analgesic agents by the intravenous route improves patient comfort and satisfaction. The consultants strongly support the importance of intravenous access in reducing patient risks. In situations when sedative/analgesic medications are to be administered intravenously, it is the consensus of the Task Force that maintaining intravenous access until the patient is no longer at risk for cardiorespiratory depression improves patient safety. In those situations when sedation is begun by nonintravenous routes (e.g., oral, rectal, intramuscular), the need for intravenous access is not sufficiently addressed in the literature. However, initiation of intravenous access after the initial sedation takes effect allows additional sedative/analgesic and resuscitation drugs to be administered if necessary.
Recommendations: In patients receiving intravenous medications for sedation/analgesia, vascular access should be maintained throughout the procedure and until the patient is no longer at risk for cardiorespiratory depression. In patients who have received sedation/analgesia by nonintravenous routes or whose intravenous line has become dislodged or blocked, practitioners should determine the advisability of establishing or reestablishing intravenous access on a case-by-case basis. In all instances, an individual with the skills to establish intravenous access should be immediately available.
XII. Reversal Agents
Specific antagonist agents are available for the opioids (e.g., naloxone) and benzodiazepines (e.g., flumazenil). The literature supports the ability of naloxone to reverse opioid-induced sedation and ventilatory depression during sedation/analgesia. However, the Task Force reminds practitioners that acute reversal of opioid-induced analgesia may result in pain, hypertension, tachycardia, or pulmonary edema. The literature supports the ability of flumazenil to reverse benzodiazepine-induced sedation and its effectiveness in reversing ventilatory depression in patients who have received benzodiazepines alone. In patients who have received both benzodiazepines and opioids, published data support the ability of flumazenil to reverse sedation; however, there are insufficient data to establish the effectiveness of flumazenil in reversing ventilatory depression under these circumstances. The consultants strongly support the contention that the availability of reversal agents is associated with decreased risk. It is the consensus of the Task Force that respiratory depression should be initially treated with supplemental oxygen and, if necessary, positive pressure ventilation by mask.
Recommendations: Specific antagonists should be available whenever opioid analgesics or benzodiazepines are administered for sedation/analgesia. Naloxone and/or flumazenil may be administered to improve spontaneous ventilatory efforts in patients who have received opioids or benzodiazepines, respectively. This may be especially helpful in cases in which airway control and positive pressure ventilation are difficult. Before or concomitantly with pharmacologic reversal, patients who become hypoxemic or apneic during sedation/analgesia should: (1) be encouraged or stimulated to breathe deeply, (2) receive positive pressure ventilation if spontaneous ventilation is inadequate, and (3) receive supplemental oxygen. After pharmacologic reversal, patients should be observed long enough to ensure that cardiorespiratory depression does not recur.
XIII. Recovery Care
Patients may continue to be at significant risk for complications after their procedure is completed. Decreased procedural stimulation, prolonged drug absorption after oral or rectal administration, and post-procedure hemorrhage may contribute to cardiorespiratory depression. When sedation/analgesia is administered to outpatients, one must assume there will be no medical supervision once the patient leaves the medical facility. Although there is not sufficient literature to examine the effects of post-procedure monitoring on patient outcomes, the consultants suggest that appropriate monitoring of patients during the recovery period will improve patient comfort and strongly support the view that adverse outcomes may be reduced. It is the consensus of the Task Force that discharge criteria should be established that minimize the risk for cardiorespiratory depression after patients are released from observation by trained personnel.
Recommendations: After sedation/analgesia, patients should be observed until they are no longer at increased risk for cardiorespiratory depression. Vital signs and respiratory function should be monitored at regular intervals until patients are suitable for discharge. Discharge criteria should be designed to minimize the risk of central nervous system or cardiorespiratory depression after discharge from observation by trained personnel (Table 4template 4).
XIV. Special Situations
The literature suggests, the consultants strongly support, and the Task Force members concur that certain classes of patients (e.g., uncooperative patients; extremes of age; severe cardiac, pulmonary, hepatic, renal, or central nervous system disease; morbid obesity; sleep apnea; pregnancy; drug or alcohol abuse) are at increased risk for developing complications related to sedation/analgesia unless special precautions are taken. However, the consultants support the view that risks may be reduced by preprocedure consultation with appropriate specialists (e.g., cardiologist, pulmonologist, nephrologist, obstetrician, pediatrician, anesthesiologist) before administration of sedation/analgesia to these individuals. The consultants support the concept that patient comfort is improved and risks are reduced by consultation with an anesthesiologist before administering sedation/analgesia to patients who are likely to develop complications (e.g., inadequate spontaneous ventilation, loss of airway control, cardiovascular compromise) or in whom sedation/analgesia alone is not expected to provide adequate conditions (e.g., young children, uncooperative patients). However, the consultants also support the contention that such consultation will not reduce costs.
Recommendations: Whenever possible, appropriate medical specialists should be consulted before administration of sedation/analgesia to patients with significant underlying conditions. The choice of specialists depends on the nature of the underlying condition and the urgency of the situation. For significantly compromised patients (e.g., severe obstructive pulmonary disease, coronary artery disease, congestive heart failure) or if it appears likely that sedation to the point of unresponsiveness or general anesthesia will be necessary to obtain adequate conditions, practitioners who are not specifically qualified to provide these modalities should consult an anesthesiologist.
Appendix 1: Methods and Analyses
The scientific assessment of these guidelines was based on the following statements or evidence linkages. These linkages represent directional hypotheses about relationships between sedation/analgesia by non-anesthesiologists and clinical outcomes.
1. A preprocedure patient evaluation (i.e., history, physical examination, laboratory evaluation) improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
2. Preprocedure preparation of the patient (e.g., counseling, fasting) improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
3. Patient monitoring (i.e., level of consciousness, pulmonary ventilation, oxygenation, hemodynamics) improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
4. Contemporaneous recording of monitored parameters (e.g., level of consciousness, respiratory function, hemodynamics) improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
5. Availability of a staff person dedicated solely to patient monitoring and safety improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
6. Education and training of (sedation/analgesia) providers improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
7. Availability of appropriately sized emergency and airway equipment, including trained staff, improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
8. Use of supplemental oxygen improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
9. Use of multiple sedative/analgesic agents improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
10. Titration of sedative/analgesic medications to achieve the desired effect improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
11. Administration of sedative/analgesic agents by the intravenous route improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
12. Availability of reversal agents (e.g., naloxone, flumazenil) improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
13. Post-procedure monitoring (e.g., during duration of recovery stay, postdischarge) improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
14. Special regimens for patients with special problems (e.g., uncooperative patients; extremes of age; severe cardiac, pulmonary, hepatic, renal, or central nervous system disease; morbid obesity; sleep apnea; pregnancy; drug or alcohol abuse; emergency/unprepared patients; metabolic and airway difficulties) improves patient satisfaction, increases clinical benefits, and reduces adverse outcomes.
Scientific evidence was derived from multiple sources, including aggregated research literature (with metaanalyses when appropriate), surveys, open presentations, and other consensus-oriented activities. For purposes of literature aggregation, potentially relevant clinical studies were identified via electronic and manual searches of the literature. The electronic search covered a 29 yr, from 1966 through 1994. Manual searches covered 48 yr, from 1947 through 1994. More than 3,000 citations were initially identified, yielding 1,315 nonoverlapping articles that addressed topics related to the 14 evidence linkages. After review of the articles, 1,046 studies did not provide direct evidence and were subsequently eliminated, yielding 269 articles containing direct linkage-related evidence. Journals represented by the 269 articles included the following disciplines: anesthesiology, 59; oncology, 5; cardiology, 12; oral/maxillofacial/dental, 71; emergency medicine, 19; gastroenterology, 50; lithotripsy, 4; obstetrics/gynecology, 5; pediatrics, 4; pharmacology, 7; pulmonary medicine, 4; radiology, 17; surgery, 8; and urology, 4.
A directional result for each study was initially determined by classifying the outcome as: (1) supporting a linkage, (2) refuting a linkage, or (3) neutral. The results were averaged to obtain a directional assessment of support for each linkage. The literature relating to linkages 8 (supplemental oxygen); 9 (multiple agents); and 12a, 12b, and 12c (naloxone to reverse opioids, flumazenil to reverse benzodiazepines, and flumazenil to reverse benzodiazepines combined with opioids, respectively) contained enough studies with well defined experimental designs and statistical information to conduct formal metaanalyses. Combined probability tests were applied when studies reported continuous data, and an odds-ratio procedure was applied to dichotomous study results.
Two combined probability tests were employed as follows: (1) the Fisher combined test, producing chi-square values based on logarithmic transformations of the reported P values from the independent studies, and (2) the Stouffer combined test, providing representation of the studies by weighting each of the standard normal deviates by the size of the sample. A procedure based on the Mantel-Haenszel method for combining study results using 2 x 2 tables was used when sufficient outcome frequency information was available. An acceptable significance level was set at P < 0.01 (one-tailed), and effect size estimates were calculated. Interobserver agreement was established through assessment of interrater reliability testing. Tests for heterogeneity of the independent samples were conducted to ensure consistency among the study results. To control for potential publishing bias, a "failsafe" N value was calculated for each combined probability test. No search for unpublished studies was conducted, and no reliability tests for locating research results were done.
Results of the combined probability tests are reported in Table 1. Significance levels from the weighted Stouffer combined tests for clinical efficacy were P < 0.001 for four linkages: 9 (multiple agents), 12a (naloxone for opioid reversal), 12b (flumazenil for benzodiazepine reversal), and 12c (flumazenil for benzodiazepine-opioid combinations). Weighted effect size estimates ranged from r = 0.20 to r = 0.42, demonstrating small-to-moderate effect size estimates. Significance levels from the weighted Stouffer combined tests for beneficial outcomes were P < 0.001 for two linkages, 8 (supplemental oxygen) and 12a (naloxone). Significance levels for adverse outcomes (P < 0.001) were found for linkage 9 (multiple agents). Linkage 12b was not significant. Weighted effect size estimates ranged from r = 0.30 to r = 0.36. Sufficient data were available to conduct Mantel-Haenszel analyses for linkages 8 (supplemental oxygen) and 9 (multiple agents). Significant differences in the odds of hypoxemia (assessed by SpO2levels) were found between patients breathing supplemental oxygen versus those breathing room air (odds ratio 4.68, 99% confidence limits 4.13-5.23, Z = 6.51, P < 0.001). The odds of an adverse outcome for multiple agents were found to be nonsignificant.
Tests for heterogeneity of statistical tests and effect size were non-significant in all cases (P > 0.01) except linkage 9 (multiple agents) and 12c (flumazenil to reverse benzodiazepines combined with opioids), indicating that the majority of pooled studies provided common estimates of significance and population effect sizes for the linkages. The two significant effect size estimates for heterogeneity may be due to a variety of factors (e.g., methodologic differences among the various studies), dissimilar outcome measures, or other mediating effects.
Agreement among Task Force members and two methodologists was established by interrater reliability testing. Agreement levels using a kappa statistic for two-rater agreement pairs were as follows: (1) type of study design, kappa = 0.69-0.95; (2) type of analysis, kappa = 0.48-0.81; (3) evidence linkage assignment, kappa = 0.65-0.90; and (4) literature inclusion for database, kappa = 0.35-1.00. Three-rater chance-corrected agreement values were: (1) design, Sav= 0.79, Var (Sav) = 0.06; (2) analysis, Sav= 0.61, Var (Sav) = 0.06; (3) linkage identification, Sav= 0.74, Var (Sav) = 0.01; and (4) literature inclusion, Sav= 0.53, Var (Sav) = 0.02. These values represent moderate to high levels of agreement.
The findings of the literature analyses were supplemented by the opinions of Task Force members and surveys of the opinions of a panel of consultants drawn from the following specialties in which sedation/analgesia are commonly administered: anesthesiology, 9; cardiology, 5; dental anesthesiology, 3; dermatology, 1; emergency medicine, 3; gastroenterology, 6; hematology/oncology, 2; intensive care, 2; oral and maxillofacial surgery, 5; pediatric dentistry, 2; pediatric oncology, 1; pharmacology, 2; plastic surgery, 1; pulmonary medicine, 5; radiology, 8; surgery, 4; and urology, 2. Consultants, in general, were highly supportive of the linkages (i.e., agreed that they resulted in improvement of patient comfort/satisfaction, reduced risk of adverse outcomes, reduced overall costs, and were important issues for the guidelines to address). Responses were given on a 5-point scale, ranging from 1, strongly disagree, to 5, strongly agree; support for a linkage was defined as the fraction of consultants responding "4" or "5" to a given linkage. The percentage of consultants reporting support for each linkage is reported in Table 2. Additional responses from consultants are listed as follows: (1) percentage of consultants supporting continuous electrocardiographic monitoring of different classes of patients was, for all patients, 23%; patients with hypertension, 51%; patients with cardiovascular disease, 91%; and patients with cardiac dysrhythmias, 94%; (2) percentage of consultants supporting the immediate availability of a defibrillator for different classes of patients was: for all patients, 64%; patients with hypertension, 68%; patients with cardiovascular disease, 83%; and patients with dysrhythmias, 85%; and (3) percentage of consultants supporting determination of vital signs and respiratory variables at the following times was: before sedation, 91%; immediately after sedation initiated, 79%; at regular intervals during procedure, 83%; at beginning of recovery, 89%; at intervals during recovery, 81%; and just before discharge, 87%.
The feasibility of implementing these guidelines into clinical practice was assessed by an opinion survey of those respondents from the consultant panel who were non-anesthesiologists (N = 37). Responses for feasibility of implementation of the guidelines were as follows: Seventy-five percent of these consultants indicated that implementation of the guidelines would not result in the need to purchase new equipment, supplies, or pharmaceuticals. Among the 25% who stated that purchases would be required, the median anticipated cost was $3,750 (mean $6,167; range $1,500-$20,000). Anticipated new costs included: hiring and training (e.g., ACLS) personnel, the presence of a nurse during procedures, establishing intravenous access as a routine procedure, exhaled carbon dioxide monitoring equipment, defibrillator, more attention to preprocedure needs (e.g., NPO status), and additional personnel time during recovery.
The non-anesthesiologist consultants were asked to indicate which, if any, of the evidence linkages would change their clinical practices if the guidelines were instituted. Percentages of consultants expecting no change associated with each linkage were as follows: preprocedure history, 81%; preparation of the patient, 76%; direct monitoring of respiration, 89%; automated ventilatory monitoring, 38%; pulse oximetry, 95%; cardiovascular monitoring, 95%; patient-dedicated staff, 89%; education and training, 95%; emergency equipment, 95%; supplemental oxygen, 95%; multiple classes of agents, 95%; titration, 92%; i.v. access, 89%; reversal agents, 92%; post-procedure monitoring, 89%; and preprocedure consultation with an anesthesiologist, 84%.
Sixty-six percent of the respondents indicated that the guidelines would have no effect on the amount of time spent on a typical case. None reported that the guidelines would reduce the amount of time spent per case. For all respondents, the mean increase in the amount of time spent on a typical case was 4.8 min. Of the 32% of respondents who reported an anticipated increase in time spent on a typical case, the mean was 14.0 min (range 5.0-30.0 min).
Readers with special interest in the statistical analyses used in establishing these guidelines can receive further information by writing to: Jeffrey B. Gross, M.D., Department of Anesthesiology (M/C 2015). University of Connecticut School of Medicine, Farmington, Connecticut 06030-2015.
Appendix 2: Definition of Terms
In these guidelines, the following terms are used to express the strength of the evidence relating various interventions and the associated outcomes.
Insufficient data: There are insufficient published data to provide an indication of the relationship between intervention and outcome.
Suggests: There is qualitative evidence in the form of case reports or descriptive studies, but there is insufficient quantitative evidence to establish a statistical relationship between intervention and outcome.
Supports: Quantitative data indicate a significant relationship between intervention and outcome (P < 0.01), and qualitative data are supportive.
The consultants' questionnaire was based on a 5-point scale ranging from "1" (strongly disagree) to "5" (strongly agree), with a score of "3" being neutral.
Suggests: The number of individuals responding "4" or "5" exceeds the number responding "1" or "2."
Supports: 50% or more of the responses were "4" or "5."
Strongly supports: 50% or more of the responses were "5."
Appendix 3: Summary of Guidelines*
Focused physical examination (to include heart, lungs, airway)
Laboratory testing when indicated
Risks, benefits, limitations, and alternatives
Sufficient time for gastric emptying
Urgent or emergent situations
Benefits of sedation/analgesia must be weighed against the potential risk of regurgitation and aspiration of gastric contents
Data to be recorded at appropriate intervals before, during, and after procedure
Response to verbal commands when practical
Pulmonary ventilation (observation, auscultation, other means)
Blood pressure and heart rate at appropriate intervals
Electrocardiograph for patients with significant cardiovascular disease
Designated individual, other than the practitioner performing the procedure, present to monitor the patient throughout the procedure
Pharmacology of sedative and analgesic agents
Pharmacology of available antagonists
Basic life support skills present
Advanced life support skills immediately available
Suction, appropriately sized airway equipment, means of positive-pressure ventilation
Intravenous equipment, pharmacologic antagonists, and basic resuscitative medications
Oxygen delivery equipment available
Oxygen administered if hypoxemia occurs
Choice of agents
Sedatives to decrease anxiety, promote somnolence
Analgesics to relieve pain
Medications given incrementally with sufficient time between doses to assess effects
Appropriate dose reduction if both sedatives and analgesics are used
Sedatives administered intravenously, maintain intravenous access
Sedatives administered by other routes, case-by-case decision
Observation until patients are no longer at risk for cardiorespiratory depression
Appropriate discharge criteria
Severe underlying medical problems, consult with appropriate specialist
Risk of severe cardiovascular or respiratory compromise or need for deep sedation/general anesthesia to obtain adequate operating conditions, consult anesthesiologist
* This is a summary of the guidelines. The body of the document should be consulted for complete details.